Cholesterol calculi are concretions comprising generally at least 40% cholesterol which generally may develop in hollow organs or ducts within humans and animals. Examples of common cholesterol calculi are cholesterol biliary duct stones and gallstones in the gallbladder. The presence of these stones within the body presents numerous health problems as would be known to those skilled in the art.
Various methods exist for removing cholesterol calculi from the bodies of humans and animals including surgery or in vivo dissolution of a calculus by the introduction of solvents into the body area where the body calculus resides. The hazards and complications attributable to surgery are well known to those skilled in the art. Thus, the advantages of avoiding or mitigating treatment by surgery for this condition are obvious.
Dissolution of cholesterol calculis in vivo has been undertaken with limited success, however, prior to the present invention. Prior to the present invention mono-octanoin (MO) has been the preferred agent for safe in vivo dissolution of cholesterol calculi in the biliary duct but has not been reported to be effective for stones in the gall bladder. The methods used for employing mono-octanoin to date for this purpose usually require 3 to 21 days of treatment. Recently it has been shown that the effectiveness of mono-octanoin as a cholesterol biliary duct stone solvent can be increased up to about four-fold by in vivo stirring or agitation and can be increased up to about 15-fold with the additional exclusion of bile, whereby the treatment time is reduced to about 1/3 to 1/4 the time required for the prior treatment with MO. These results are described and explained in the present inventors co-pending U.S. patent application entitled, "In Vivo Method for Distributing and Stirring of Therapeutic Agents," Ser. No. 599,398, filed Apr. 10, 1984, as well as in abstracts of papers appearing in: Gastroenterology, Volume 84, No. 5, Part 2, Page 1090, 1983; Hepatology, Volume 3, No. 5, Abstract No. 44, Page 809, 1983. The entire disclosure of these references is incorporated herein by reference.
Although these techniques for using MO can reduce the time needed to dissolve biliary duct stones, the time required for such treatment is still relatively long, particularly when the stones are relatively large and/or are not too well positioned, in vivo, for such treatment.
Diethyl ether has a cholesterol solubilizing capacity similar to MO (13.7 g/100 cc vs. 11.7 g/100 cc) but dissolves cholesterol gallstones much more rapidly than does MO. Diethyl ether, however, immediately vaporizes at its boiling point of 34.5.degree. C. and expands its volume 120-fold. It is thus not useful for in vivo purposes.
A need still exists, therefore, for therapeutic agents and solvents which can dissolve cholesterol calculi, in vivo, including biliary duct stones in a shorter period of time than that provided for by the use of MO.
The advantages which can be derived from the use of more effective and time efficient solvents for the in vivo dissolution of cholesterol calculi include a reduction of the patient's discomfort during the introduction of the solvent in vivo, which is often via a catheter or other needle-like structure, as well as a reduction in the time the patient may be exposed to the risk of infection or other possible deleterious side effects of a treatment of this type, as well as being subject to a shorter hospital stay.